Prognostic Value of Autoantibodies in Predicting Arthritis Progression

Patients with clinically suspect arthralgia who have circulating anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are at an increased risk of clinical arthritis progression, according to research presented at the American College of Rheumatology 2016 annual meeting.

Robin M ten Brinck, PhD candidate from the Department of Rheumatology at Leiden University Medical Center, the Netherlands, and colleagues evaluated 255 patients with clinically suspect arthalgia  within the past 12 months who were considered at risk of developing rheumatoid arthritis (RA)  according to their physicians.

Over a follow-up period of 96 weeks, patients who with suspect arthralgia were monitored for serological positivity for immunogloubin M-rheumatoid factor (IgM-RF), ACPA, and anti-carbamylated protein to determine what factors contributed to development of clinical arthritis.

Of the patients who were ACPA and RF positive, 45 developed clinical arthritis. Specifically, patients who subsequently developed arthritis were more likely to be RF positive (hazard ratio [HR] = 4.8; 95% CI, 2.7 – 8.7), ACPA positive (HR=7.9, 95%CI=4.4-14.3), and anti-carbamylated protein positive (HR = 3.7, 95% CI = 1.9 – 7.3).

Only ACPA-seropositivity remained significantly associated with future arthritis development after multivariable Cox regression analyses (HR=5.0, 95%CI=1.9-12.9).

Among patients with RF positive and ACPA positive, the highest HR was 9.5 (95% confidence interval [CI], 4.9 – 18.3), compared with patients who are both RF-negative and ACPA-negative. There were no significant differences between patients who were RF-positive and patients who were RF-negative.

Although nearly 70% of ACPA-positive RF-positive patients progressed to having clinical arthritis, 30% did not develop clinical arthritis during a median follow-up duration of 96 weeks.

”Patients with clinically suspect arthralgia experience arthralgia of metacarpophalangeal, proximal interphalangeal or wrist joints that, according to the rheumatologist, is suspect to progress to rheumatoid arthritis. However, no clinical arthritis is yet detectable at psychical examination at baseline,” Dr ten Brinck told Rheumatology Advisor in an interview.

“Within patients with clinically suspect arthralgia, anti–citrullinated protein antibody (ACPA)—possibly in combination with rheumatoid factor (RF)—was associated with increased risks on progression to clinical arthritis. However, 33% of the ACPA-positive/RF-positive patients does not progress to clinical arthritis within two years despite experiencing clinically suspect arthralgia. No baseline differences were found for ACPA-positive/RF-positive patients that did progress and did not progress to clinical arthritis. This indicates that information on autoantibodies alone is insufficient to adequately predict autoantibody-positive rheumatoid arthritis.”


ten Brinck RM, van Steenbergen HW, Verheul MK, et al. The prognostic value of different auto-antibodies for arthritis development in patients with clinically suspect arthralgia. Presented at: ACR/ARHP Annual Meeting; November 11-16, 2016; Washington D.C. Abstract #1035.

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